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Velders G.J.M.,National Institute of Public Health and the Environment RIVM | Geilenkirchen G.P.,PBL Netherlands Environmental Assessment Agency | de Lange R.,TNO
Atmospheric Environment | Year: 2011

In past years, the European limit value for average annual NO 2 concentration has been exceeded in city streets and along motorways in the Netherlands. By 2015 the limit value must be adhered to in the Netherlands. Although the total road length for which exceedance is likely is expected to decrease over the coming years, exceedances may still occur by 2015. Future NO 2 concentrations not only depend on economic growth, current and proposed policies, and on inevitable meteorological fluctuations, they also depend on the effectiveness of technical measures to reduce emissions. New emission measurements for heavy-duty vehicles in the Euro-V (and Euro-III) emission standard categories, carried out under typical Dutch driving conditions, have revealed that real-world NO x emissions from these trucks are significantly higher than was previously estimated based on the reduction steps in the Euro emission standards. Emission levels were higher, by about a factor of three, along city streets, and 10 to 40% higher along motorways. These higher emission levels resulted in higher estimated national NO x emissions, increasing from 250kt to 264kt, compared with the national emission ceiling of 260kt, to be adhered to by 2010. The higher emissions more than double the total road length with possible exceedance (chance >33%) of the NO 2 limit value; from about 100km to about 250km along cities streets and motorways, by 2015. These higher emissions from trucks, therefore, affect the chances of the limit values being adhered to, in time, everywhere in the Netherlands. © 2011 Elsevier Ltd.

Quik J.T.K.,Wageningen University | van De Meent D.,Radboud University Nijmegen | van De Meent D.,National Institute of Public Health and the Environment RIVM | Koelmans A.A.,Wageningen University
Water Research | Year: 2014

Parameters and simplified model approaches for describing the fate of engineered nanoparticles (ENPs) are crucial to advance the risk assessment of these materials. Sedimentation behavior of ENPs in natural waters has been shown to follow apparent first order behavior, a 'black box' phenomenon that is insufficiently understood and therefore of limited applicability. Here we use a detailed Smoluchowski-Stokes model that accounts for homo- and heteroaggregation and sedimentation of ENPs and natural colloids (NCs), to simulate and interpret experimental ENP aggregation-sedimentation data. The model adequately simulated the observed time and initial concentration dependence of CeO2 settling data, and also predicted the conditions for aggregation rate-limitations of overall removal. Heteroaggregation with natural colloids was identified as the dominating removal process. Finally, the empirical apparent first order model data were calibrated against the mechanistic Smoluchowski-Stokes model simulation data, showing excellent fits for a range of NC initial concentrations. Using first order removal rates thus can be considered a valid and informed approximation when modeling ENP fate in the aquatic environment. © 2014 Elsevier Ltd.

Slob W.,National Institute of Public Health and the Environment RIVM
Critical Reviews in Toxicology | Year: 2014

Evaluating dose-response data using the Benchmark dose (BMD) approach rather than by the no observed adverse effect (NOAEL) approach implies a considerable step forward from the perspective of the Reduction, Replacement, and Refinement, three Rs, in particular the R of reduction: more information is obtained from the same number of animals, or, vice versa, similar information may be obtained from fewer animals. The first part of this twin paper focusses on the former, the second on the latter aspect. Regarding the former, the BMD approach provides more information from any given dose-response dataset in various ways. First, the BMDL (= BMD lower confidence bound) provides more information by its more explicit definition. Further, as compared to the NOAEL approach the BMD approach results in more statistical precision in the value of the point of departure (PoD), for deriving exposure limits. While part of the animals in the study do not directly contribute to the numerical value of a NOAEL, all animals are effectively used and do contribute to a BMDL. In addition, the BMD approach allows for combining similar datasets for the same chemical (e.g., both sexes) in a single analysis, which further increases precision. By combining a dose-response dataset with similar historical data for other chemicals, the precision can even be substantially increased. Further, the BMD approach results in more precise estimates for relative potency factors (RPFs, or TEFs). And finally, the BMD approach is not only more precise, it also allows for quantification of the precision in the BMD estimate, which is not possible in the NOAEL approach. © 2014 Informa Healthcare USA, Inc.

Slob W.,National Institute of Public Health and the Environment RIVM
Critical Reviews in Toxicology | Year: 2014

OECD test guidelines for standard toxicity studies prescribe (minimal) numbers of animals, but these are not substantiated by a quantitative analysis of the relationship between number of animals and the required performance of the associated study design. This paper provides a general approach of how this relationship may be established and discusses the approach in more detail by focusing on the three typical repeated-dose studies (subacute, subchronic, and chronic). Quantitative results derived from simulation studies, including some new results, are summarized and their consequences for study guidelines are discussed. The currently prescribed study designs for repeated-dose studies do not appear to be sufficient when the NOAEL is used for evaluating the data-the probability of not detecting toxicologically significant effects is high. The ensuing need for increasing the number of animals may be avoided by replacing the NOAEL approach by the BMD approach as it increases the probability of detecting the same effects without increasing the number of animals. Hence, applying the BMD approach will result in a virtual reduction in the number of animals. Further, the BMD approach allows for a real reduction in the number of animals on various grounds. It allows for analyzing combined similar datasets, resulting in an increase in precision, which can be translated in animal reduction while keeping the same precision. In addition, applying the BMD approach may be expected to result in animal reduction in the long run, as it allows for distributing the same number of animals over more doses without loss of precision. The latter will reduce the need to repeat studies due to unfortunate dose location. © 2014 Informa Healthcare USA, Inc.

Heijstek M.W.,University Utrecht | Van Gageldonk P.G.M.,National Institute of Public Health and the Environment RIVM | Berbers G.A.M.,National Institute of Public Health and the Environment RIVM | Wulffraat N.M.,University Utrecht
Annals of the Rheumatic Diseases | Year: 2012

Objectives: To compare the persistence of measles, mumps, rubella, diphtheria and tetanus antibodies between patients with juvenile idiopathic arthritis (JIA) and healthy controls. Methods: Measles, mumps, rubella (MMR) and diphtheria-tetanus toxoid (DT)-specific immunoglobulin G antibody concentrations were compared between 400 patients with JIA and 2176 healthy controls aged 1-19 years. Stored patient samples from the period 1997-2006 were obtained from one Dutch centre for paediatric rheumatology. Healthy control samples had been evaluated previously in a nationwide cohort. Participants had been vaccinated according to the Dutch immunisation programme. Antibody concentrations were measured by ELISA (MMR) or multiplex immunoassay (DT). Results: Corrected for age and the number of vaccinations, lower vaccine-specific geometric mean antibody concentrations (GMC) were found in patients with JIA against mumps, rubella, diphtheria and tetanus (p≤0.001). Measles-specific GMC were higher (p<0.001) compared with healthy controls. The prevalence of protective antibody concentrations was significantly lower in patients for mumps (OR 0.4; 95% CI 0.3 to 0.6), rubella (OR 0.4; 0.3 to 0.7), diphtheria (OR 0.1; 0.06 to 0.2) and tetanus (OR 0.1; 0.05 to 0.3). Seroprotection rates against measles did not differ between patients and healthy controls (OR 1.4; 0.8 to 2.5). Methotrexate and glucocorticosteroid use did not affect pathogen-specific GMC or seroprotection rates. Conclusions: Patients with JIA had lower antibody concentrations and seroprotection rates than healthy controls against mumps, rubella, diphtheria and tetanus, but not measles. In these patients, regular assessment of antibody concentrations and further research on responses to other (booster) vaccines are warranted.

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